The concept of the autistic spectrum (or the autism spectrum) is largely used but seems poorly understood by people in general. In this video I explain how it came about and what it actually means.
The Autism Spectrum: Explained
Autism – Star cells in the brain render memory flexible
Increasing calcium in hippocampal astrocytes induces co-release of D-serine and glutamate through Best1. Glutamate released from CA3 neurons can induce local norepinephrine release by activating presynaptic AMPAR in the LC terminal. The astrocytes increase the NMDAR tone, which is important for homo- and hetero-synaptic long-term depression (LTD) in nearby synapses. CREDIT Institute for Basic Science
“The measure of intelligence is the ability to change” – Albert Einstein
As we live in a dynamically changing environment, it is important for our brain to not only learn new things but also to modify existing memories. This is commonly referred to as “cognitive flexibility”. Without this ability, we would not be able to adapt to the altered environment and be vulnerable to making wrong choices from relying only on past memories.
Led by Director C. Justin LEE, the researchers at the Center for Cognition and Sociality within the Institute for Basic Science (IBS) in Daejeon, South Korea reported that astrocytes, which are star-shaped cells in the brain, regulate cognitive flexibility. Specifically, they found that the astrocytes’ ability to simultaneously regulate and integrate synaptic plasticity of nearby synapses is important for facilitating cognitive flexibility.
It is thought that lower cognitive flexibility in brain disorders such as autism, schizophrenia, and early stages of Alzheimer’s disease is caused by the reduced function of N-methyl-D-aspartate receptors (NMDARs). While NMDARs are important receptors for synaptic plasticity and are activated by a number of agonists and co-agonists, the source of one of the co-agonists, D-serine, has been controversial. Using astrocyte-specific gene regulation, the researchers showed that astrocytes can actually synthesize D-serine and release it through the calcium-activated channel called Best1. Combined with the previous knowledge that astrocytes can release glutamate through Best1, the co-release of D-serine and glutamate indicates that astrocytes are ideal regulators of NMDAR activity and synaptic plasticity.
In particular, the researchers showed that heterosynaptic long-term depression (LTD), a phenomenon in which inactive synapses weaken when nearby synapses become active, is mediated by astrocytes and is critical for cognitive flexibility.
“Since each astrocyte is in contact with over 100,000 synapses, astrocytes can control numerous synapses and integrate synaptic plasticity simultaneously,” said KOH Wuhyun, the first author of this study.
In the report, they studied the Best1 knockout (Best1 KO) mouse model that lacks heterosynaptic LTD due to reduced NMDAR tone. In the Morris Water Maze experiment, which involves mice trying to find a hidden platform, Best1 KO mice performed similarly to the wild-type mice in the initial learning session. However, when the platform was relocated to the opposite side, Best1 KO mice exhibited problems in memory modification.
Interestingly, when the NMDAR tone was improved in Best1 KO mice by D-serine injection during the initial learning period, their memory modification problem was restored in the subsequent experiment. This discovery shows that memory flexibility is determined from the time of initial learning, which is different from the previously proposed theory that synaptic plasticity only occurs when memory modification is needed.
Additionally, the researchers discovered that norepinephrine and its receptor α1-AR can activate astrocytes and cause co-release of D-serine and glutamate. This implies that the flexibility of memory can be determined by the degree of concentration and arousal during the learning period.
Director C. Justin LEE stated, “Previous studies have mostly focused on changes in specific synapses to stimuli. The discovery of this phenomenon where changes in one synapse can induce changes in nearby synapses during learning shows that finding out what happens to the other synapses is important for understanding the mechanism of learning and memory formation.” He added, “It is hoped that this study will provide valuable insights on how to relieve or treat symptoms of autism, schizophrenia, and early dementia, which are known to reduce cognitive flexibility.”
Ketamine therapy swiftly reduces depression and suicidal thoughts
Ketamine therapy has a swift short-term effect on reducing symptoms of depression and suicidal thoughts, according to a review of all the available evidence.
A systematic review led by the University of Exeter and funded by the Medical Research Council analysed evidence from 83 published research papers. The strongest evidence emerged around the use of ketamine to treat both major depression and bipolar depression. Symptoms were reduced as swiftly as one to four hours after a single treatment, and lasted up to two weeks. Some evidence suggested that repeated treatment may prolong the effects, however more high-quality research is needed to determine by how long
Similarly, single or multiple doses of ketamine resulted in moderate to large reductions in suicidal thoughts. This improvement was seen as early as four hours following ketamine treatment and lasted on average three days, and up to a week
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Lead author Merve Mollaahmetoglu, of the University of Exeter, said: “Our research is the most comprehensive review of the growing body of evidence on the therapeutic effects of ketamine to date. Our findings suggest that ketamine may be useful in providing rapid relief from depression and suicidal thoughts, creating a window of opportunity for further therapeutic interventions to be effective. It’s important to note that this review examined ketamine administration in carefully controlled clinical settings where any risks of ketamine can be safely managed.
For other psychiatric disorders, including anxiety disorders, post-traumatic stress disorders and obsessive-compulsive disorders, there is early evidence to suggest the potential benefit of ketamine treatment. Moreover, for individuals with substance use disorders, ketamine treatment led to short-term reductions in craving, consumption and withdrawal symptoms.
Published in the British Journal of Psychiatry Open, the review synthesises the evidence from a growing field of research into the potential benefits of ketamine for conditions for which there are limited effective treatments. The review included 33 systematic reviews, 29 randomised control trials, and 21 observational studies.
Ketamine’s effects on depressive symptoms and suicidal thoughts are supported by numerous systematic reviews and meta-analyses, which provide an exhaustive overview of research in a given topic. These are considered to have the highest strength of evidence compared to other types of studies, increasing confidence in the evidence for ketamine’s antidepressant and anti-suicidal effects.
However, ketamine’s therapeutic effects for psychiatric conditions other than depression and suicidal thoughts are based on small number of studies that did not randomise people into different treatment arms. These effects require replication in larger randomised placebo-controlled trials, which are considered as gold standard.
The authors noted a number of difficulties in the research field, which they recommend that future studies should seek to address. One factor is the bias created because participants realise they have been given ketamine, rather than a saline solution. Senior author Professor Celia Morgan, of the University of Exeter, said: “We’re finding that ketamine may have promising benefits for conditions that are notoriously hard to treat in clinic. We now need bigger and better-designed trials to test these benefits. For example, due to ketamine’s unique subjective effects participants may be able to tell whether they have been given ketamine or a saline solution as the placebo, potentially creating an expectation about the effects of the drug. This effect may be better controlled by having active placebo-controlled trials, where the control group receives another drug with psychoactive properties.”
A number of questions remain unanswered in the research field, including the optimal dose, route of administration and number of doses of ketamine treatment. There is also a need for further research on the added and interactive benefit of psychotherapy alongside ketamine treatment.
Additionally, the importance of ketamine’s acute subjective effects in its therapeutic benefits has not been fully explored. More research is also needed on how to optimise participants’ preparation for ketamine treatment and the setting in which ketamine treatment is delivered.
The research involved collaboration with the University of British Columbia, and received support from the Society for the Study of Addiction. The paper is entitled ‘Ketamine for the treatment of mental health and substance use disorders: a comprehensive systematic review’, and is published in the British Journal of Psychiatry Open.
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Cochlear implant in autistic deaf children can improve language skills and social engagement
Restoring hearing through cochlear implantation for children with autism can help them understand spoken language and enhance social interactions, according to a study from Ann & Robert H. Lurie Children’s Hospital of Chicago. The study reported long-term outcomes of the largest number of children with autism who received a cochlear implant, with mean follow-up of 10.5 years. Findings were published in the journal Otology & Neurotology.
“Our results add to the growing body of evidence that cochlear implantation clearly benefits deaf children with autism spectrum disorder,” said senior author Nancy Young, MD, Medical Director of Audiology and Cochlear Implant Programs at Lurie Children’s and a Professor of Pediatric Otolaryngology at Northwestern University Feinberg School of Medicine. “Improved hearing provides access to spoken language that may enhance their cognitive and communication potential, as well as help these children engage more with their families.”
The majority (73 percent) of children in the study consistently used their cochlear implant throughout the day, of whom 45 percent developed some understanding of spoken words with hearing alone (no visual cues). Forty five percent also used spoken language to some degree as part of their overall communication. Eighty six percent were reported by parents to have improved social engagement after implantation. Responding to a survey, one parent reported: “Without his implant, he was stuck in his own little world, no sound, no eye contact with others. The implant brought his personality out to us.”
According to recent estimates, one in 88 children in the US have autism , a complex developmental disorder characterized by impaired communication and social interaction. Twenty-five to 30 percent of normal hearing children with autism do not develop spoken language as a means of communication. Therefore, children with autiusm in combination with profound hearing loss have two conditions that may limit development of spoken language. Not surprisingly, the children in this study usually developed understanding and use of spoken language more slowly than implanted children without autuism .
Children with autism have been reported to have a higher prevalence of sensorineural hearing loss (SNHL) than children without autism . Conversely, children with SNHL have been reported to have a higher rate of autism than those with normal hearing. Dr. Young noted that “the relationship between these two diagnoses for some of these children may be due to congenital cytomegalovirus (CMV), an infection that begins in the developing fetus that often is unrecognized after birth. It may cause hearing loss and is associated with increased incidence of autism .”
Most children in the study were diagnosed with autism after cochlear implantation. Diagnosis after implantation is likely related to the young age at which most received their implant, and to increased difficulty diagnosing autism when significant hearing loss is present.
“Understanding the range of outcomes in this population is important for counseling parents and educators to ensure that these children receive appropriate support and services,” said Beth Tournis, AuD, an audiologist at Lurie Children’s and co-author of the study.